Generic Name and Formulations:
Tezacaftor, ivacaftor 100mg/150mg; with ivacaftor 150mg; tabs.
Indications for SYMDEKO:
Treatment of cystic fibrosis (CF) in patients ≥12yrs who are homozygous for the F508del mutation or have ≥1 mutation in the CFTR gene that is responsive to tezacaftor/ivacaftor.
Swallow whole. Take with fat-containing food (eg, eggs, cheeses, nuts, whole milk, meats). 1 tab (100mg/150mg) in the AM and 1 tab (150mg) in the PM, approx. 12hrs apart. Concomitant moderate CYP3A inhibitors (eg, fluconazole, erythromycin): alternate 1 tab (100mg/150mg) in the AM or 1 tab (150mg) in the AM every other day. Concomitant strong CYP3A inhibitors (eg, ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin): 1 tab (100mg/150mg) in the AM twice weekly, approx. 3–4 days apart. Hepatic impairment (moderate): 1 tab (100mg/150mg) once daily; (severe): 1 tab (100mg/150mg) once daily, or less frequently; use with caution.
If genotype is unknown, use an FDA-cleared CF mutation test to detect the presence of the CFTR mutation followed by bi-directional sequencing verification. Assess ALT/AST and bilirubin levels prior to initiating therapy, every 3 months during the first year of treatment, and annually thereafter. History of transaminase elevations; consider more frequent monitoring. Interrupt dosing and monitor closely if ALT/AST is >5×ULN or if ALT/AST is >3×ULN with bilirubin elevations >2×ULN; after resolution, consider restarting. Severe hepatic impairment. Perform baseline and follow-up eye exams. Severe renal impairment or ESRD. Pregnancy. Nursing mothers.
Potentiated by strong or moderate CYP3A inhibitors; adjust dose (see Adult). Avoid food or drink containing grapefruit or Seville oranges. Concomitant strong CYP3A inducers (eg, rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort): not recommended. Caution with concomitant digoxin or other P-gp substrates with a narrow therapeutic index (eg, cyclosporine, everolimus, sirolimus, tacrolimus): monitor.
Cystic fibrosis transmembrane conductance regulator (CFTR) corrector + CFTR potentiator.
Headache, nausea, sinus congestion, dizziness; transaminase elevations.